Optically active N-(halopropyl)amino acid derivatives are used for, for example, synthesizing optically active cyclic amino acids that are of use as synthetic intermediates of medicines, agrochemicals, and the like.
For such a method for synthesizing an optically active N-(halopropyl)amino acid derivative, Japanese Laid-Open Patent Publication No. 2005-82572 and T. Kawabata et al., “Journal of the American Chemical Society (J. Am. Chem. Soc.)”, 2003, Vol. 125, pp. 13012-13013 disclose a method in which an optically active amino acid derivative and a halogenated alcohol (specifically, bromopropanol) are reacted to give an optically active N-(hydroxypropyl)amino acid derivative, the nitrogen atom of the obtained compound is protected by introducing a protecting group, and then the hydroxyl group is substituted with a halogen atom.
O. V. Bykhovskaya et al., “Russian Chemical Bulletin, International Edition”, November 2005, Vol. 54, pp. 2642-2647 discloses a method for synthesizing a racemic N-(3-chloropropyl)alanine ethyl ester from ethyl bromoacetate and 3-chloropropylamine hydrochloride. This allows an N-(halopropyl)amino acid derivative to be produced.
However, the methods of Japanese Laid-Open Patent Publication No. 2005-82572 and T. Kawabata et al., “Journal of the American Chemical Society (J. Am. Chem. Soc.)”, 2003, Vol. 125, pp. 13012-13013 use expensive bromopropanol as a starting material and require a step of substituting a hydroxyl group with a halogen atom. Furthermore, in order to use the obtained N-(hydroxypropyl)amino acid derivative as an intermediate in a subsequent step, a purification step with column chromatography or the like is also necessary. Moreover, since the N-(3-chloropropyl)alanine ethyl ester obtained according to the method disclosed in O. V. Bykhovskaya et al., “Russian Chemical Bulletin, International Edition”, November 2005, Vol. 54, pp. 2642-2647 is a racemate, a step of optical resolution is necessary to obtain an optically active form thereof. Further, even if an acetate, which is a starting material, is processed in advance into its optically active form, it is not clear whether the optical activity is maintained after the reaction with an amine salt.